The proposed pilot study is designed to retrospectively investigate field cancerization in patients with multiple primary nonmelanoma skin cancer (NMSC) of the head and neck. It is hypothesized that accumulated exposure to external carcinogens, such as solar ultraviolet radiation and chemical mutagens. results in a "field" or area of skin that is predisposed to neoplastic growth. Numerous cells in the field independently enter the early stages of carcinogenesis due to distinct genetic alterations and with time a subset of these cells progress to primary tumors. Therefore, the field is "condemned" to the development of multiple primary neoplasms. In order to provide molecular evidence for field cancerization of the head and neck skin, we plan to analyze mutations in the p53 tumor suppressor gene in multiple primary NMSCs and adjacent tissues from patients who have been previously treated at the University of Texas M. D. Anderson Cancer Center. Clinical and epidemiologic information on these patients will be integrated with the molecular data in order to gain insight on the etiology of the disease and provide a basis for the design of large case control studies on the risk factors associated with the disease. The importance of determining whether field cancerization occurs in the head and neck skin lies in the fact that isolated tumors and initiated fields require different treatment protocols. The treatment of multiple primary NMSC of the head and neck is often protracted by the need for repeated surgical resection, and the morbidity and medical costs associated with the disease are substantial. Thus the prevention of multiple tumor development in cancerized fields should prove to be a very effective component of disease management. The results of our study will provide a rational basis for further investigations on treatments that contain or reverse the multistep process of progression to multiple primary NMSC.